Abstract
Background50% of leprosy patients suffer from episodes of Type 1/ reversal reactions (RR) and Type 2/ Erythema Nodosum Leprosum (ENL) reactions which lead to morbidity and nerve damage. CD4+ subsets of Th17 cells and CD25+FOXP3+ regulatory T cells (Tregs) have been shown to play a major role in disease associated immunopathology and in stable leprosy as reported by us and others. The aim of our study was to analyze their role in leprosy reactions.Methodology and Principle FindingsQuantitative reverse transcribed PCR (qPCR), flowcytometry and ELISA were used to respectively investigate gene expression, cell phenotypes and supernatant levels of cytokines in antigen stimulated PBMC cultures in patients with stable disease and those undergoing leprosy reactions. Both types of reactions are associated with significant increase of Th17 cells and associated cytokines IL-17A, IL-17F, IL-21, IL-23 and chemokines CCL20, CCL22 as compared to matching stable forms of leprosy. Concurrently patients in reactions show reduction in FOXP3+ Treg cells as well as reduction in TGF-β and increase in IL-6. Moreover, expression of many T cell markers, cytokines, chemokines and signaling factors were observed to be increased in RR as compared to ENL reaction patients.ConclusionsPatients with leprosy reactions show an imbalance in Th17 and Treg populations. The reduction in Treg suppressor activity is associated withhigherTh17cell activity. The combined effect of reduced TGF-β and enhanced IL-6, IL-21 cytokines influence the balance between Th17 or Treg cells in leprosy reactions as reported in the murine models and autoimmune diseases. The increase in Th17 cell associated cytokines may contribute to lesional inflammation.
Highlights
Leprosy reactions occurring in approximately 50% of leprosy patients cause severe morbidity and need immediate clinical attention
The combined effect of reduced TGF-β and enhanced IL-6, IL-21 cytokines influence the balance between Th17 or Treg cells in leprosy reactions as reported in the murine models and PLOS Neglected Tropical Diseases | DOI:10.1371/journal.pntd
The study group included 30 leprosy patients in reactions prior to institution of anti-reaction therapy: 15 each were in type 1/reversal reactions (RR) and type 2/Erythema Nodosum Leprosum (ENL); 36 freshly diagnosed patients with stable leprosy without previous history or clinical evidence of reactions were included as controls and consisted of 18 each of borderline tuberculoid (BT) and lepromatous (LL) leprosy
Summary
Leprosy reactions occurring in approximately 50% of leprosy patients cause severe morbidity and need immediate clinical attention. Tuberculoid leprosy presents as both polar (TT) and borderline (BT) forms with well defined an aesthetic skin patches which are paucibacillary and prone to early peripheral nerve damage. Leprosy reactions are mainly of 2 types, Type 1 or reversal reactions (RR) are seen in borderline leprosy forms of BT, BB and BL where there is inflammation localized to the dermal patch and the neighboring peripheral nerve[3]. Type 2 reaction specially ENL, appears in BL/LL patients who show systemic features accompanied by fever, joint pains and small reddish nodules scattered over the body along with peripheral nerve involvement. Patients at the tuberculoid and lepromatous poles show reverse patterns in cell mediated immunity and antibody responses to the M.leprae antigens and have been reported to be associated respectively with Th1, Th2 paradigm[4] with some patients showing Th0 profile[5]. The triggering factors in the inductions of these reactions are not known motifs of LSR2protein of M.leprae have been shown to be recognized during ENL[8]
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